Using our recently described in vitro transformation assay for the bovine papilloma virus and for its molecularly cloned genomic DNA, mouse cells transformed either by virus or by viral DNA have been shown to contain multiple unintegrated viral DNA copies in the absence of detectable integrated viral DNA. Efficient transformation by the p21 (src) coding region of Harvey murine sarcoma virus (Ha-MuSV) DNA requires that the viral long terminal repeat (LTR) be ligated to the p21 coding region. Two independent p21 coding genes have been cloned from normal rat cell DNA; one gene is colinear with the viral p21 coding region, while the second gene contains intervening sequences. When the Ha-MuSV LTR is ligated to either gene, it can transform NIH3T3 cells, associated with high intracellular p21 levels. The origin and formation of mink cytopathic focus-forming (MCF) murine leukemia viruses (MuLV) has also been studied. Endogenous MCF-like viral DNAs have been found in AKR and other mouse strains. The entire env of some non-pathogenic MCF viruses has apparently been derived from these sequences. In spontaneous murine thymic tumors, one or more of these MCF-like sequences have regularly recombined with a specific region of the 3' end of ecotropic env. Pathogenic MCF viruses also contain these ecotropic virus-derived recombinant sequences.